Infection and Drug Resistance (May 2023)

TBX5 Variants are Associated with Susceptibility to and the Incidence of Liver Cirrhosis and Hepatocellular Carcinoma in the Chinese Population: A Multicenter and Follow-Up Study

  • Yao J,
  • Mao X,
  • Sun Q,
  • Wu B,
  • Yu W,
  • Huang Y,
  • Luo S,
  • Zeng J,
  • Lin J

Journal volume & issue
Vol. Volume 16
pp. 2653 – 2665

Abstract

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JinJian Yao,1,2,* Xiaochun Mao,3,* Qigang Sun,4,* Biao Wu,5 Weiling Yu,6 Yanjing Huang,7 Shuai Luo,1 Jia Zeng,1 Jusheng Lin2 1Department of Emergency, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 2Institute of Liver and Gastrointestinal Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Ophthalmology, Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 5Infectious Disease, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 6Oncology Department, Haikou City People’s Hospital, Haikou, Hainan, People’s Republic of China; 7Oncology Department of Hainan General Hospital, Haikou, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: JinJian Yao; Jusheng Lin, Email [email protected]; [email protected]: Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are progressions affected by genetic predispositions, and persistent hepatitis B virus infection also demonstrates genetic susceptibility. All HBV-related outcomes have been compared in parallel to identify risk polymorphism in HBV progression.Methods: The multiple-stage association study filtered and validated the risk SNPs for HBV progression and explored their association with persistent infection, with a total of 8906 subjects in China from three sites. Cox proportional hazards models and Kaplan–Meier Log rank tests were used to determine the time to the progressive event in relation to the risk SNPs.Results: Rs3825214 in TBX5 replicated a specific association with LC and HCC in 4 progression cohorts and was not related to persistent infection, naivety to HBV infection and natural clearance in 3 persistent cohorts. In combined samples, rs3825214 was associated with an increased risk of LC (P< 0.001; OR = 1.98) and HCC (P< 0.001; OR = 1.68). The results of bioinformatics analysis indicated that rs3825214 genotypes change RNA structure and intron excision ratio. In the follow-up of 571 hospital-based persistent HBV infection patients, ninety-three (16.29%) developed LC, and seventy-four (12.96%) progressed to HCC at a median follow-up of 5.1 years. Rs3825214 was associated with HCC and LC events in Cox proportional hazards models (P< 0.001).Conclusion: We identified and confirmed that genetic variants in TBX5 are significantly associated with susceptibility to and the incidence of LC and HCC.Keywords: TBX5, polymorphism, liver cirrhosis, hepatocellular carcinoma, follow-up, hepatitis B virus

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